Clinical interpretation of reference intervals and reference limits. A plea for assay harmonization

George G. Klee

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


Reference intervals for healthy subjects and diseased populations are important benchmarks for the clinical interpretation of laboratory test values. It is important that the testing conditions used to collect the reference data be closely matched with the testing conditions used for patient data. Interlaboratory differences and intralaboratory changes, especially changes in analytic set-points, can markedly affect the clinical interpretation of tests. If laboratory testing methods could be harmonized, laboratories could potentially share reference data to make these data more reliable. This chapter illustrates the use of reference intervals for healthy subjects and reference data from diseased populations for medical decisions. One example illustrates the effects of age differences on test result interpretation. Other examples illustrate use of thyroid-stimulating hormone (TSH) and combinations of TSH with free thyroxine measurements for diagnosing thyroid diseases. Both univariate and multivariate reference intervals are discussed. Model systems for using disease prevalence and cost utility functions are provided to illustrate optimization of medical decisions.

Original languageEnglish (US)
Pages (from-to)752-757
Number of pages6
JournalClinical Chemistry and Laboratory Medicine
Issue number7
StatePublished - 2004


  • Decision limits
  • Harmonization
  • Normal values
  • Reference intervals
  • Reference limits

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical


Dive into the research topics of 'Clinical interpretation of reference intervals and reference limits. A plea for assay harmonization'. Together they form a unique fingerprint.

Cite this